Relationship BetweenERCC1Polymorphisms, Disease Progression, and Survival in the Gynecologic Oncology Group Phase III Trial of Intraperitoneal Versus Intravenous Cisplatin and Paclitaxel for Stage III Epithelial Ovarian Cancer

Abstract

Purpose We hypothesized that common polymorphisms in excision repair cross-complementation group 1 (ERCC1), involved in nucleotide excision repair of platinum-induced damage, would be associated with progression-free survival (PFS) and overall survival (OS) in women with optimally resected, stage III epithelial ovarian cancer (EOC) treated with cisplatin and paclitaxel (C + P). Patients and Methods Single nucleotide polymorphism analysis was carried out by direct pyrosequencing at two sites (codon 118 and C8092A) in ERCC1 in leukocyte DNA from women who participated in the Gynecologic Oncology Group (GOG) phase III protocol-172 and were randomly assigned to intraperitoneal or intravenous C + P Results ERCC1 genotyping was performed in 233 of the 429 women who participated in GOG-172. The genotype distribution at codon 118 was 17% with C/C, 43% with C/T, and 40% with T/T, and the genotype distribution at C8092A was 56% with C/C, 37% with C/A, and 7% with A/A. Adjusted Cox regression analysis revealed that the codon 118 polymorphism in ERCC1 was not significantly associated with disease progression or death. Women with the C8092A C/A or A/A genotypes compared with the C/C genotype had an increased risk of disease progression (hazard ratio [HR] = 1.44; 95% CI, 1.06 to 1.94; P = .018) and death (HR = 1.50; 95% CI, 1.07 to 2.09; P = .018). Median PFS and OS were 6 and 17 months shorter for women with the C8092A C/A or A/A genotypes versus the C/C genotype, respectively. Conclusion Although the ERCC1 codon 118 polymorphism does not seem to be associated with clinical outcome, the C8092A polymorphism was an independent predictor of PFS and OS in women with optimally resected EOC.

Xeroderma pigmentosum complementation group C single‐nucleotide polymorphisms in the nucleotide excision repair pathway correlate with prolonged progression‐free survival in advanced ovarian cancer

“…Two SNPs in the ERCC1 gene (rs11615 and rs3212986) have been correlated with platinum response in ovarian cancer in recently published studies, although the results were discrepant. 11,28 These SNPs, which also were evaluated in our study, did not produce significant associations with platinum response. However, because of the important role of XPF in DNA repair and the significance of the in vitro data as a heterodimer with ERCC1, SNPs in XPF and in the ERCC1 gene may lead to significant genetic variability in patients' response to platinum chemotherapy and should be included in future studies.…”

“…Only a few studies have examined the role of SNPs in the NER pathway in both ovarian cancer risk and response to chemotherapy. [9][10][11][12][13][14] Those studies demonstrated that variants in the xeroderma pigmentosum (XP) complementation family group of proteins can predict platinum sensitivity and survival outcomes. 9,10 Because of the potential importance of the NER pathway, we sought to determine whether single-nucleotide polymorphisms in this pathway could be a prognostic marker of response to platinum-based chemotherapy in ovarian cancer.…”

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

“…Particularly interesting is the SNP T19007C:rs11615 in codon 118, which has been associated with response rate and/or overall survival in patients diagnosed with colorectal cancer (17,18). In other tumor types, including HNSCC, however, this association was not consistently demonstrated (19)(20)(21)(22).…”

Overexpression of S100A14 in human serous ovarian carcinoma

“…EOC accounts for 85-90% of clinical ovarian malignancies, and SOC is the main type of EOC (45). At present, excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) is a key topic of studies attempting to predict chemotherapy resistance in ovarian cancer (46,47). The current criteria for evaluating chemoresistance against platinum are based on unchanged tumor size responding to the first-line therapy strategy, tumor progression during chemotherapy, and recurrence within six months post-chemothrapy (48).…”